Retroviruses form a large class of enveloped RNA viruses which invade a large number of specific mammalian hosts. They are infectiously transmitted by a variety of mechanisms, are frequently associated with severe diseases, and share common elements among their structures. The retroviruses, consisting of a (+) strand RNA dimer (ssRNA), form long terminal repeats ("LTR") in their proviral DNA intermediates and a genome coding for capsid proteins ("the gag gene"), reverse transcriptase and integrase functions (the "pol" gene), and the membrane envelope gene ("env"). With particular viruses, other open reading frames have been shown to be present coding for proteins having specific functions in addition to the functions of the common genes.
Feline leukemia viruses (FeLV) are exogenous type C retroviruses that are responsible for induction of a diverse series of lymphoreticular diseases of outbred cats including lymphosarcoma, leukemia, aplastic anemia, myelodysplasia, and feline acquired immunodeficiency syndrome (Hardy et al., Cancer Res. 36:582, 1976; Hardy, Feline Leukemia Virus, Hardy, Essex, McCelland, eds. (Elsevier/North Holland, 1980), pp. 3-31; Hoover, Rojko, Olsen, Feline Leukemia, Olsen, ed. (CRC Press, Boca Raton, Fla., 1980), pp. 32-51; Hardy and Essex, Prog. Allergy 37:353, 1986). The genome of FeLV is a 60-70S dimer of single-stranded RNA consisting of a gag gene encoding the capsid proteins, a pol gene encoding the protease, reverse transcriptase and integrase, and an env gene encoding the gp70 and p15E viral envelope proteins. As with other retroviruses, when a susceptible cell is infected with FeLV (in vivo or in vitro), the genome is transcribed into a double-stranded DNA copy which is then carried in the cellular DNA as a provirus organized into 5'-LTR (long terminal repeat)-gag-pol-env-LTR-31' regions. The integrated provirus then serves as the template for production of FeLV RNAs and ultimately infectious virions.
FeLV have been classified into subgroups A, B, and C on the basis of virus interference and neutralization assays, and the distribution of the subgroups within feline populations differs markedly. Subgroup A viruses have been found in all naturally occurring infections examined, either alone or in combination with B and C. Subgroup B, found in approximately 40% of all infections, and subgroup C, found in perhaps 1% of infections, occur as mixed infections of subgroups A and B, A and C, or A, B, and C. Subgroup identity also correlates with the host range of infection in vitro and pathogenicity in cats: FeLV-A isolates are sometimes restricted to growth in feline cells and are minimally pathogenic; FeLV-B isolates grow in heterologous cells such as human and canine fibroblastoid cells and are found at a higher frequency in cats with proliferative disease; and the rare FeLV-C isolates have an extended host range including human, canine, and guinea pig cells and are capable of inducing aplastic anemia.
In view of the devastating effect of FeLV-induced disease in domestic cats, the prevention of FeLV infection through vaccination of susceptible animals is a high priority for veterinary researchers. Numerous attempts to produce such a vaccine have been largely unsuccessful and, in fact, the only commercially available vaccine (Leukocell.TM., Norden Laboratories, Lincoln, Nebr.) has been severely criticized for its questionable efficacy (Pedersen et al., Feline Practice 15:7-20, 1985). The present invention fulfills the need in the art for a suitable FeLV vaccine, and further provides other related advantages, including the definition of a prototype highly infectious FeLV-A challenge virus, a prototype molecularly cloned immunodeficiency inducing FeLV, and a disease model useful for the study of retrovirus-induced immunodeficiency syndrome and leukemia in cats and humans.